The goal of this project is to understand the molecular lesions which result in a deficiency in globin synthesis in the various thalassemia syndromes. Current effort is concentrated on studying transcription of the individual globin genes in chromatin and the processing of RNA in the nucleus. Chromatin from patients with beta thalassemia is transcribed in vitro and the relative synthesis of alpha and beta globin mRNA sequences is determined. Nuclear RNA is isolated and the relative sequence ratio for alpha and beta globin mRNA is determined in various size fractions and compared to that found in the cytoplasm.